Towards a better understanding of the different release phases from PLGA microparticles: Dexamethasone-loaded systems

Dexamethasone-loaded, poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared using an oil-in-water solvent extraction/evaporation method. The drug loading was varied from 2.4 to 61.9%, keeping the mean particle size in the range of 52-61 μm. In vitro drug release was characterized by up to 3 phases: (1) an (optional) initial burst release, (2) a phase with an about constant drug release rate, and (3) a final, again rapid, drug release phase. The importance and durations of these phases strongly depended on the initial drug loading. To better understand the underlying mass transport mechanisms, the microparticles were thoroughly characterized before and after exposure to the release medium. The initial burst release seems to be mainly due to the dissolution of drug particles with direct access to the microparticles' surface. The extent of the burst was negligible at low drug loadings, whereas it exceeded 60% at high drug loadings. The second release phase seems to be controlled by limited drug solubility effects and drug diffusion through the polymeric systems. The third drug release phase is likely to be a consequence of substantial microparticle swelling, leading to a considerable increase in the systems' water content and, thus, fundamentally increased drug mobility.

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